[unreadable] [unreadable] Biorepositories are a valuable resource in translational research for cancer and there are many such repositories in both academic and industrial settings. While these repositories are valuable, they are not immune from cost constraints and the approach to storing biological specimens (e.g., serum and plasma) involves a fundamental cost tradeoff between storing the samples in a larger number of vials each with volumes (100 [unreadable]l to 400 [unreadable]l) suitable for assaying or storing the samples in larger volumes (2 ml or 4 ml) to save freezer space. The first approach avoids downstream aliquotting and has only one freeze/thaw cycle but requires labor to aliquot the fresh sample and is volumetrically inefficient. The second approach requires aliquotting when the samples are requested and as a result the sample experiences a freeze/thaw cycle when it is processed for a study but is volumetrically efficient. A hybrid approach is also pursued where fresh samples are initially stored in a volumetrically efficient format until they are requested for a study and then returned to storage in the volumetrically inefficient format to avoid subsequent freeze/thaw cycles. This project will develop an automated instrument that will offer a new approach, combining the volumetrically efficient storage with the single freeze/thaw cycle. This instrument will extract aliquots from frozen samples without thawing the samples. Not only will this approach reduce the cost of operating these repositories while eliminating the second freeze/thaw cycle associated with the hybrid approach, but because it is automated it will increase the throughput in processing samples, reducing the 6 1/2 weeks to one week for a 1000 sample study, which is typical for the Nurses' Health Study. This team has demonstrated the ability to: (1) maintain the sample at -70 oC during processing; (2) extract aliquots from normal saline frozen at -80 oC, and (3) manage frost buildup during the procedure. The R21 project and the milestones have been developed to address the key technical risks associated with this instrument and the R33 project will deliver a prototype instrument that is suitable for use by the Nurses' Health Study to process samples for their collaborators. The design at this point will be documented well enough to enable its production in our lab in small quantities for use in other biorepositories. [unreadable] [unreadable]